2024
TRPM8 Mutations Associated With Persistent Pain After Surgical Injury of Corneal Trigeminal Axons
Ghovanloo M, Effraim P, Tyagi S, Aldrich A, Cheng X, Yuan J, Schulman B, Jacobs D, Dib-Hajj S, Waxman S. TRPM8 Mutations Associated With Persistent Pain After Surgical Injury of Corneal Trigeminal Axons. Neurology Genetics 2024, 10: e200206. PMID: 39555137, PMCID: PMC11567650, DOI: 10.1212/nxg.0000000000200206.Peer-Reviewed Original ResearchLaser-assisted in situ keratomileusisPostoperative ocular painTrigeminal ganglion neuronsOcular painMultielectrode array recordingsPersistent painGanglion neuronsLaser-assisted in situ keratomileusis surgeryAxonal injuryRat trigeminal ganglion neuronsTransient receptor potential cation channelCorneal refractive surgeryMultielectrode arraysAnalysis of patientsPatch-clamp analysisGenomic analysis of patientsWild-typePatch-clamp resultsExposure to mentholRefractive surgeryHyperpolarizing directionNeuronal hyperexcitabilityPain-freeTrigeminal axonsWT channels
2023
Nav1.7 P610T mutation in two siblings with persistent ocular pain after corneal axon transection: impaired slow inactivation and hyperexcitable trigeminal neurons
Ghovanloo M, Effraim P, Yuan J, Schulman B, Jacobs D, Dib-Hajj S, Waxman S. Nav1.7 P610T mutation in two siblings with persistent ocular pain after corneal axon transection: impaired slow inactivation and hyperexcitable trigeminal neurons. Journal Of Neurophysiology 2023, 129: 609-618. PMID: 36722722, PMCID: PMC9988530, DOI: 10.1152/jn.00457.2022.Peer-Reviewed Original ResearchConceptsPersistent ocular painTrigeminal ganglion neuronsOcular painCorneal refractive surgeryGanglion neuronsRefractive surgeryAxonal injurySlow inactivationHuman pain modelTrigeminal afferent nervesTrigeminal ganglion axonsSmall subgroupPain-related disordersEffects of injurySodium channel Nav1.7Channel slow inactivationEye painPostoperative painMost patientsPain modelAfferent nervesPersistent painTrigeminal neuronsNav1.7 mutationAxon transection
2021
KCNQ variants and pain modulation: a missense variant in Kv7.3 contributes to pain resilience
Yuan JH, Estacion M, Mis MA, Tanaka BS, Schulman BR, Chen L, Liu S, Dib-Hajj FB, Dib-Hajj SD, Waxman SG. KCNQ variants and pain modulation: a missense variant in Kv7.3 contributes to pain resilience. Brain Communications 2021, 3: fcab212-. PMID: 34557669, PMCID: PMC8454204, DOI: 10.1093/braincomms/fcab212.Peer-Reviewed Original ResearchPluripotent stem cell-derived sensory neuronsNav1.7 mutationSensory neuronsPain ProfilePain phenotypesPain resilienceDorsal root ganglion neuronsDaily pain diaryPeripheral sensory neuronsMissense variantsVoltage-clamp recordingsSodium channel Nav1.7Different pain experiencesPotential genetic factorsWhole-exome sequencingLarger M-currentsErythromelalgia patientsNeuropathic painPain episodesModerate painPain diaryPain modulationSevere painInter-individual variabilityGanglion neurons
2019
A Novel Gain-of-Function Nav1.9 Mutation in a Child With Episodic Pain
Huang J, Estacion M, Zhao P, Dib-Hajj FB, Schulman B, Abicht A, Kurth I, Brockmann K, Waxman SG, Dib-Hajj SD. A Novel Gain-of-Function Nav1.9 Mutation in a Child With Episodic Pain. Frontiers In Neuroscience 2019, 13: 918. PMID: 31551682, PMCID: PMC6733892, DOI: 10.3389/fnins.2019.00918.Peer-Reviewed Original ResearchDorsal root gangliaDRG neuronsEpisodic painVoltage-gated sodium channel Nav1.9Episodic abdominal painLarger window currentSmall DRG neuronsTrigeminal ganglion neuronsCurrent-clamp recordingsAction potential firingHuman pain disordersVoltage-clamp recordingsChronic constipationAbdominal painMyenteric neuronsPain disordersGanglion neuronsPain phenotypesRoot gangliaCommon painNav1.9PainAction potentialsWindow currentPhenotypic spectrum
2018
Resilience to Pain: A Peripheral Component Identified Using Induced Pluripotent Stem Cells and Dynamic Clamp
Mis MA, Yang Y, Tanaka BS, Gomis-Perez C, Liu S, Dib-Hajj F, Adi T, Garcia-Milian R, Schulman BR, Dib-Hajj SD, Waxman SG. Resilience to Pain: A Peripheral Component Identified Using Induced Pluripotent Stem Cells and Dynamic Clamp. Journal Of Neuroscience 2018, 39: 382-392. PMID: 30459225, PMCID: PMC6335750, DOI: 10.1523/jneurosci.2433-18.2018.Peer-Reviewed Original ResearchMeSH KeywordsAdultChildChronic PainErythromelalgiaExcitatory Postsynaptic PotentialsExomeFemaleGanglia, SpinalHumansImmunohistochemistryIndividualityInduced Pluripotent Stem CellsKCNQ Potassium ChannelsMaleMembrane PotentialsNAV1.7 Voltage-Gated Sodium ChannelPain MeasurementPatch-Clamp TechniquesResilience, PsychologicalSensory Receptor CellsConceptsWhole-exome sequencingPeripheral sensory neuronsSensory neuronsSpecific gene variantsGene variantsPluripotent stem cell-derived sensory neuronsInterindividual differencesDorsal root ganglion neuronsExome sequencingDifferent pain profilesDRG neuron excitabilityDynamic clampPeripheral nervous systemStem cellsPain ProfilePluripotent stem cellsChronic painPeripheral mechanismsGanglion neuronsNeuron excitabilityPainNervous systemHuman genetic modelsNeuronsDifferent gene variantsA novel gain-of-function Nav1.7 mutation in a carbamazepine-responsive patient with adult-onset painful peripheral neuropathy
Adi T, Estacion M, Schulman BR, Vernino S, Dib-Hajj S, Waxman S. A novel gain-of-function Nav1.7 mutation in a carbamazepine-responsive patient with adult-onset painful peripheral neuropathy. Molecular Pain 2018, 14: 1744806918815007. PMID: 30392441, PMCID: PMC6856981, DOI: 10.1177/1744806918815007.Peer-Reviewed Original ResearchConceptsPainful peripheral neuropathyDorsal root gangliaPeripheral neuropathyUse-dependent inhibitionDRG neuronsPain disordersM variantFunction Nav1.7 mutationsMulti-electrode array recordingsSympathetic ganglion neuronsCommon pain disordersVoltage-clamp recordingsVoltage-gated sodium channel NaRare MendelianNav1.7 mutationGanglion neuronsSodium channel NaTrigeminal ganglionRoot gangliaNeonatal ratsPatientsNeuropathyMutant channelsFunction variantsNeurons
2016
Nav1.7-A1632G Mutation from a Family with Inherited Erythromelalgia: Enhanced Firing of Dorsal Root Ganglia Neurons Evoked by Thermal Stimuli
Yang Y, Huang J, Mis MA, Estacion M, Macala L, Shah P, Schulman BR, Horton DB, Dib-Hajj SD, Waxman SG. Nav1.7-A1632G Mutation from a Family with Inherited Erythromelalgia: Enhanced Firing of Dorsal Root Ganglia Neurons Evoked by Thermal Stimuli. Journal Of Neuroscience 2016, 36: 7511-7522. PMID: 27413160, PMCID: PMC6705539, DOI: 10.1523/jneurosci.0462-16.2016.Peer-Reviewed Original ResearchConceptsRat DRG neuronsDorsal root ganglion neuronsDRG neuronsCurrent-clamp recordingsSodium channel Nav1.7Pain syndromeNav1.7 mutationGanglion neuronsThermal stimuliIEM patientsChannel Nav1.7Whole-cell current-clamp recordingsNav1.7 channelsFunction Nav1.7 mutationsSevere pain syndromeVoltage-gated sodium channel Nav1.7Voltage-clamp recordingsMutant Nav1.7 channelsMean firing frequencyMultielectrode array recordingsMutant channelsG mutationMultigeneration familySpontaneous firingSympathetic neuronsPharmacotherapy for Pain in a Family With Inherited Erythromelalgia Guided by Genomic Analysis and Functional Profiling
Geha P, Yang Y, Estacion M, Schulman BR, Tokuno H, Apkarian AV, Dib-Hajj SD, Waxman SG. Pharmacotherapy for Pain in a Family With Inherited Erythromelalgia Guided by Genomic Analysis and Functional Profiling. JAMA Neurology 2016, 73: 659. PMID: 27088781, DOI: 10.1001/jamaneurol.2016.0389.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAdultAnalgesics, Non-NarcoticBrainCarbamazepineChronic PainDNA Mutational AnalysisDouble-Blind MethodElectric StimulationErythromelalgiaFemaleGanglia, SpinalHumansMagnetic Resonance ImagingMaleMutationNAV1.7 Voltage-Gated Sodium ChannelPain MeasurementRegression AnalysisSensory Receptor CellsConceptsMean episode durationDRG neuronsPatient 1Nav1.7 mutationEpisode durationDorsal root ganglion neuronsPlacebo-controlled studyMaintenance periodAttenuation of painEffects of carbamazepineBrain activityFunctional magnetic resonance imagingMagnetic resonance imagingT mutationMutant channelsFunctional magnetic resonanceNeuropathic painSecondary somatosensoryChronic painPain areaPatient 2Ganglion neuronsEffective pharmacotherapyNight awakeningsPlacebo